PURPOSE OF THE STUDY: Septic arthritis (SA) constitutes an orthopaedic emergency as it can rapidly lead to progressive and irreversible joint destruction with loss of function. We aim to identify our microbiological spectrum and sensitivity profiles, and compare it to our empirical antimicrobial choice in the management of septic arthritis in the adult population. DESCRIPTION OF METHODS: A retrospective analysis was performed on patients admitted from June 2005 to March 2009. The study population consisted of all patients over the age of 14 years admitted for either arthrotomies or joint aspirations, yielding positive cultures of either joint fluid or pus swabs taken intra-operatively. A data analysis was also done on serum CRP and WCC on all the patients. SUMMARY OF RESULTS: Gram-positive organisms were cultured in only 53% of isolates, and Staphylococcus aureus accounted for only 25% of all isolates. Of all the Gram-positive organisms, 38% were multi-drug resistant, only sensitive to vancomycin. Gram-negative organisms constituted 36% of isolates, showing resistance in 55%. The remainder of isolates consisted of anaerobic organisms. CONCLUSION: Gram-negative and resistant strains are becoming more important as an aetiological agent in adult septic arthritis. The current use of cloxacillin as empiric antibiotic therapy only covers 32% of all isolates in our setting. Based on these findings, use of co-amoxyclav as empiric antibiotic will increase the cover to 46%. The emergence of resistant strains remains a challenge, as evidenced by this study. Patients not responding to initial empiric therapy should be considered for early use of extended spectrum antimicrobials.